The objective of this research project is to investigate the physiogenetic basis of lymphoiesis, reticulum cell hyperplasia, and immune responses. We will use two lines of mice that were developed through inbreeding and selective breeding for difference in leukocyte production. The high leukocyte count (HLC) and low eukocyte count (LLC) lines differ in lymphocyte production by sevenfold, as well as in a number of biological characteristics that are fixed genetically. We will study the pathology and progression of reticulum cell hyperplasia and polydipsia, both of which are characteristic of LLC mice. Examining the mice at various stages of aging for possible development of leukemia, we will test for differences between these lines with respect to their response to carcinogens. Preliminary results indicate that HLC and LLC mice differ in immune response to sheep red cells. We will do linkage tests to identify specific genes that affect leukocyte production on different chromosomes. For an investigation of immune response, we will produce mixed lymphocyte cultures and one-way stimulation cultures of cells of the HLC and LLC mice. In addition to further study on differences in response to sheep red cell, we intend also to test other immunogens in these lines of mice.